title: Synthesis and vaccine evaluation of the tumor-associated carbohydrate antigen RM2 from prostate cancer.
abstract: We have successfully developed a [1+2+3] one-pot strategy to synthesize the RM2 antigen hexasaccharide that was proposed to be a prostate tumor antigen. The structure of the synthetic product was verified by NMR analysis and antibody binding assay using a glycan microarray. In addition, the synthetic antigen was conjugated to a mutated diphtheria toxin (DT, CRM197) with different copy numbers and adjuvant combinations to form the vaccine candidates. After vaccination in mice, we used glycan microarrays to monitor their immune response, and the results indicated that, when one molecule of DT was incorporated with 4.7 molecules of RM2 on average (DT-RM4.7) and adjuvanted with the glycolipid C34, the combination exhibited the strongest anti-RM2 IgG titer. Moreover, the induced mouse antibodies mediated effective complement-dependent cytotoxicity (CDC) against the prostate cancer cell line LNCap.
authors.affiliation: Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 115, Taiwan.
authors.forename: Hong-Yang
authors.initials: HY
authors.lastname: Chuang
authors.forename: Chien-Tai
authors.initials: CT
authors.lastname: Ren
authors.forename: Chung-An
authors.initials: CA
authors.lastname: Chao
authors.forename: Chung-Yi
authors.initials: CY
authors.lastname: Wu
authors.forename: Sachin S
authors.initials: SS
authors.lastname: Shivatare
authors.forename: Ting-Jen R
authors.initials: TJ
authors.lastname: Cheng
authors.forename: Chung-Yi
authors.initials: CY
authors.lastname: Wu
authors.forename: Chi-Huey
authors.initials: CH
authors.lastname: Wong
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D019496:Cancer Vaccines / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D060326:Chemistry Techniques, Synthetic; D004167:Diphtheria Toxin / Q000235:genetics / Q000378:metabolism; D005690:Galactose / Q000378:metabolism; D006017:Glycolipids / Q000378:metabolism; D008297:Male; D051379:Mice; D009154:Mutation; D009844:Oligosaccharides / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000276:immunology*; D014614:Vaccines, Synthetic
chemical_list: D000276:Adjuvants, Immunologic; D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines; D004167:Diphtheria Toxin; D006017:Glycolipids; D009844:Oligosaccharides; D014614:Vaccines, Synthetic; D005690:Galactose